We propose, as a continuing multicenter collaborative group to maintain and expand our current investigations of cancer risk in relation to in utero exposure to diethylstilbestrol (DES) through the DESAD (DES-ADenosis) Project. The long-term goals are: (A) to test specific hypotheses relating to the continuing risk of genital tract neoplasia following DES exposure; (B) to investigate further major health issues relevant to the DES-exposed population; and (C) to identify and elucidate those aspects of the DESAD Project experience which are applicable to research and practice in cancer in general. The specific aims in support of these goals, to be pursued over 5 years in our active population, centering on some 5000 women with known in utero exposure status (4000 exposed, l000 nonexposed controls), relate to: (l) clear-cell adenocarcinoma, (2) squamous neoplasia, (3) vaginal adenosis and cervical epithelial changes, (4) histopathologic and cytologic studies, (5) changing risk factors for neoplasia and other abnormalities, (6) risks of in utero DES exposure to the second generation, (7) reproductive experience, and (8) other diseases and abnormalities. Participating institutions are the Baylor College of Medicine, Gundersen Foundation, Massachusetts General Hospital, Mayo Clinic, and Cedars Sinai Medical Center (Los Angeles). The investigators (gynecologists, epidemiologists, nurse practitioners, pathologists, and statisticians) will continue to follow an established detailed Manual of Procedures, with each participant seen annually for an additional 5 years. At each visit, an interval health history and breast and pelvic examinations will be recorded, as well as colposcopy, cytology, and colposcopically directed biopsies of atypical areas when indicated for detection of neoplasia or its precursors. Project data will continue to be transmitted to the coordinating center (Mayo Clinic) for keypunching, editing, general quality control, and analysis. The current program of active data monitoring and analysis and reporting of project experience will continue on a closely collaborative basis involving all centers. The study will improve understanding of factors important to the health of the DES-exposed population and should, in addition, have implications for cancer research and practice more generally, especially in relation to the female reproductive system.